A cationic bis‐imidazolium‐based amphiphile was used to form thermoreversible nanostructured supramolecular hydrogels incorporating neutral and cationic drugs for the topical treatment of rosacea. The concentration of the gelator and the type and concentration of the drug incorporated were found to be factors that strongly influenced the gelling temperature, gel‐formation period, and overall stability and morphology. The incorporation of brimonidine tartrate resulted in the formation of the most homogeneous material of the three drugs explored, whereas the incorporation of betamethasone resulted in a gel with a completely different morphology comprising linked particles. NMR spectroscopy studies proved that these gels kept the drug not only at the interstitial space but also within the fibers. Due to the design of the gelator, drug release was up to 10 times faster and retention of the drug within the skin was up to 20 times more effective than that observed for commercial products. Experiments in vivo demonstrated the rapid efficacy of these gels in reducing erythema, especially in the case of the gel with brimonidine. The lack of coulombic attraction between the gelator–host and the guest–drug seemed particularly important in highly effective release, and the intermolecular interactions operating between them were found to lie at the root of the excellent properties of the materials for topical delivery and treatment of rosacea.

Condyloma acuminata is an infectious disease caused by the human papilloma virus (HPV) and one of the most common sexually transmitted infections. It is manifested as warts that frequently cause pain, pruritus, burning, and occasional bleeding. Treatment (physical, chemical, or surgical) can result in erosion, scars, or ulcers, implying inflammatory processes causing pain. In this work, a biocompatible topical hydrogel containing 2% ketorolac tromethamine was developed to manage the painful inflammatory processes occurring upon the removal of anogenital condylomas. The hydrogel was physically, mechanically, and morphologically characterized: it showed adequate characteristics for a topical formulation. Up to 73% of ketorolac in the gel can be released following a one-phase exponential model. Upon application on human skin and vaginal mucosa, ketorolac can permeate through both of these and it can be retained within both tissues, particularly on vaginal mucosa. Another advantage is that no systemic side effects should be expected after application of the gel. The hydrogel showed itself to be well tolerated in vivo when applied on humans, and it did not cause any visible irritation. Finally, ketorolac hydrogel showed 53% anti-inflammatory activity, suggesting that it is a stable and suitable formulation for the treatment of inflammatory processes, such as those occurring upon chemical or surgical removal of anogenital warts.

Gels formed by a gemini dicationic amphiphile incorporate a serine protease inhibitor, which could be used in a new approach to the treatment of Rosacea, within the fibres as well as in the space between them, affecting a number of gel properties but most importantly inducing remarkable fibre coiling at the microscopic level as a result of drug release from the gel. Drug release and skin permeation experiments show its potential for topical administration.